The Immunology and Immunotherapy (l&l) Program represents the merger of the central components of two pre-existing programs, the basic science Immunology Program and the immunotherapy-oriented Lymphoma Program. The l&l Program's overall mission is to translate fundamental advances in our understanding of basic cancer immunology to therapeutic advances, by closely coordinating and integrating the laboratory and clinical components. This coordination is highly bidirectional, however. Insights gained in the laboratory used to inform the development of new therapies, and discoveries in the clinic are used to direct new laboratory studies. The l&l Program is built upon an exceptionally strong foundation in fundamental immunology, its members comprising an illustrious group of investigators responsible for major advances in T- and B-cell development, dendritic cell function, Toll-like receptors, and antigen presentation. Moreover, the l&l Program has produced a variety of novel immunotherapeutic approaches, encompassing a spectrum of immunologic strategies facilitated by the Program's laboratory advances, including 1) the induction of anti-tumor immunity via extracorporeal photoimmunetherapy (ECP); 2) methods of minimizing graft-versus-host disease in allogeneic stem cell transplantation; 3) optimization of graft-versus-tumor responses; 4) biodegradable nanoparticles for delivery of tumor antigen vaccines; 5) enhancement of anti-tumor immune responses by blockade of CTLA-4. The l&l Program has 46 independent but highly interactive members representing both laboratory and clinical investigators from 11 departments. The program is led by Ira Mellman (Chair, Cell Biology; YCC Associate Director for Science), bridges the fundamental and clinical l&l components. Dr. Mellman is an expert in the mechanisms of antigen presentation by DCs and more recently has focused on applying basic immunological principles to the development of human cancer immunotherapies. Three Associate Leaders, working closely with Dr. Mellman, direct subcomponents of the Program. Dr. Warren Shlomchik oversees the basic cancer immunology component, while Dr. Michael Girardi and Dr. Francine Foss have responsibility for the immunotherapy component. Communication and programmatic focus are maintained by a monthly meeting of members devoted to cancer immunology, a working group charged with implementing immunotherapy protocols, a general retreat, a seminar series, and a newly established seed grant competition to fund innovative approaches to immunotherapy. Total peer-reviewed support is $20.8 direct costs ($30.1 million total costs). Overall funding is $28.4 million in direct costs ($39.2 million total costs). In the last grant period, 613 cancerrelated papers were published, of which 23% were intraprogrammatic and 11% were interprogrammatic.